The present invention relates to the field of sample processing devices. More particularly, the present invention relates to assemblies of sample processing devices and carriers, as well as methods of using the sample processing devices.
Many different chemical, biochemical, and other reactions are sensitive to temperature variations. The reactions may be enhanced or inhibited based on the temperatures of the materials involved. In many such reactions, a temperature variation of even 1 or 2 degrees Celsius may have a significantly adverse impact on the reaction. Although it may be possible to process samples individually and obtain accurate sample-to-sample results, individual processing can be time-consuming and expensive.
One approach to reducing the time and cost of processing multiple samples is to use a device including multiple chambers in which different portions of one sample or different samples can be processed simultaneously. However, this approach presents several temperature control related issues. When using multiple chambers, the temperature uniformity from chamber to chamber may be difficult to control. Another problem involves the speed or rate at which temperature transitions occur when thermal processing, such as when thermal cycling. Still another problem is the overall length of time required to thermal cycle a sample(s).
The multiple chamber device may include a distribution system. However, the distribution system presents the potential for cross-contamination. Sample may inadvertently flow among the chambers during processing, thereby potentially adversely impacting the reaction(s) occurring in the chambers. This may be particularly significant when multiple samples are being processed. In addition, the distribution system may present problems when smaller than usual samples are available, because the distribution system is in fluid communication with all of the process chambers. As a result, it is typically not possible to prevent delivery of sample materials to all of the process chambers to adapt to the smaller volume samples.
Thermal processing, in and of itself, presents an issue in that the materials used in the devices may need to be robust enough to withstand repeated temperature cycles during, e.g., thermal cycling processes such as PCR. The robustness of the devices may be more important when the device uses a sealed or closed system.
The present invention provides methods and devices for thermal processing of multiple samples at the same time. The sample processing devices provide process arrays that include conduits useful in distributing sample materials to a group of process chambers located in fluid communication with the main conduits. The sample processing devices may include one or more of the following features in various combinations: deformable seals, process chambers connected to the main conduit by feeder conduits exiting the main conduit at offset locations, U-shaped loading chambers, and a combination of melt bonded and adhesively bonded areas.
If present in the sample processing devices of the present invention, deformable seals may provide for closure of the main conduits to prevent leakage. Deformable seals may also provide for isolation of the process chambers located along the main conduit, such that cross-contamination (e.g., migration of reagent between process chambers after introduction of sample material) between the process chambers may be reduced or eliminated, particularly during sample processing, e.g. thermal cycling. Deformable seals may also provide the opportunity to tailor the devices for specific test protocols by closing the distribution channels leading to selected process chambers before distributing sample materials. Alternatively, some deformable seals may be closed to adjust for smaller sample material volumes reducing the number of process chambers to which the sample materials are distributed.
Sample processing devices of the present invention that include feeder conduits connecting the process chambers to the main conduits may preferably do so using feeder conduits that exit the main conduit at different locations along the main conduit, such that no main conduit/feeder conduit junctions are directly aligned across the main conduit. Such an arrangement may provide further reductions in the possibility of cross-contamination between process chambers by providing a longer path length between the process chambers.
Loading structures in the form of U-shaped loading chambers, where provided, may provide advantages in filling of the loading chambers by providing a structure from which air (or any other fluid located in the loading chamber) can escape during filling.
Sample processing devices that include both melt bonded and adhesive bonded areas may provide the advantage of capitalizing on the properties of both attachment methods in a single device. For example, it may be preferred to use melt bonding in the areas occupied by the process chambers to take advantage of the strength of the melt bonds. In the same device, it may be possible to take advantage of the sealing properties of the adhesive bonded areas.
In other aspects, the sample processing devices of the present invention may be used in connection with carriers that may, in various embodiments, provide for selective compression of sample processing devices, either compression of discrete areas proximate the process chambers or compression of the sample processing devices in the areas outside of the process chambers. In various embodiments, the carriers may preferably provide for limited contact between themselves and the sample processing devices, limited contact between themselves and any compression structure used to compress the carrier and sample processing device assembly, and limited thermal mass. The carriers may also provide openings to allow visual access to the process chambers.
It is also preferred that the sample processing devices of the invention exhibit robustness in response to the rapid thermal changes that can be induced due to the relatively high thermal conductivity and relatively low thermal mass of the devices. This robustness may be particularly valuable when the devices are used in thermal cycling methods such as, e.g., PCR. In all thermal processing methods, the preferred devices maintain process chamber integrity despite the pressure changes associated with the temperature variations and despite the differences between thermal expansion rates of the various materials used in the devices.
Yet another advantage of the present invention is that the devices may be mass manufactured in a web-based manufacturing process in which the various components may be continuously formed and/or bonded, with the individual devices being separated from the continuous web.
As used in connection with the present invention, the following terms shall have the meanings set forth below.
xe2x80x9cDeformable sealxe2x80x9d (and variations thereof) means a seal that is permanently deformable under mechanical pressure (with or without a tool) to occlude a conduit along which the deformable seal is located.
xe2x80x9cThermal processingxe2x80x9d (and variations thereof) means controlling (e.g., maintaining, raising, or lowering) the temperature of sample materials to obtain desired reactions. As one form of thermal processing, xe2x80x9cthermal cyclingxe2x80x9d (and variations thereof) means sequentially changing the temperature of sample materials between two or more temperature setpoints to obtain desired reactions. Thermal cycling may involve, e.g., cycling between lower and upper temperatures, cycling between lower, upper, and at least one intermediate temperature, etc.
In one aspect, the present invention provides a sample processing assembly including a sample processing device and a carrier attached to the sample processing device. The sample processing device includes a body with a first side attached to a second side and a plurality of process arrays formed between the first and second sides. Each process array of the plurality of process arrays includes a loading structure, a main conduit with a length, a plurality of process chambers distributed along the main conduit, and a deformable seal located between the loading structure and the plurality of process chambers, wherein the main conduit is in fluid communication with the loading structure and the plurality of process chambers. The carrier includes a first surface facing the sample processing device and a second surface facing away from the sample processing device; a plurality of main conduit support rails proximate the first surface of the carrier, wherein each main conduit of the plurality of process arrays is aligned with one main conduit support rail of the plurality of main conduit support rails; and a plurality of openings formed through the first and second surfaces of the carrier, wherein each opening of the plurality of openings is aligned with one process chamber of the plurality of process chambers.
In another aspect, the present invention provides a method of processing sample materials, the method including providing a sample processing assembly that includes a sample processing device attached to a carrier. The sample processing device includes a body with a first side attached to a second side and a plurality of process arrays formed between the first and second sides. Each process array of the plurality of process arrays includes a loading structure, a main conduit with a length, and a plurality of process chambers distributed along the main conduit, wherein the main conduit is in fluid communication with the loading structure and the plurality of process chambers. Each of the process arrays also includes a deformable seal located between the loading structure and the plurality of process chambers in each process array of the plurality of process arrays. The carrier includes a first surface facing the sample processing device and a second surface facing away from the sample processing device; a plurality of main conduit support rails proximate the first surface of the carrier, wherein each main conduit of the plurality of process arrays is aligned with one main conduit support rail of the plurality of main conduit support rails; and a plurality of openings formed through the first and second surfaces of the carrier, wherein each opening of the plurality of openings is aligned with one process chamber of the plurality of process chambers. The method further includes distributing sample material to at least some of the process chambers in each process array of the plurality of process arrays through the main conduit in each of the process arrays; closing the deformable seal in each process array of the plurality of process arrays, the closing including supporting the main conduit with one of the main conduit support rails while compressing the first side and the second side of the sample processing device together along the main conduit; locating the second side of the sample processing device in contact with a thermal block; and controlling the temperature of the thermal block while the sample processing device is in contact with the thermal block.
In another aspect, the present invention provides a method of processing sample materials by providing a sample processing assembly including a sample processing device attached to a carrier. The sample processing device includes a body with a first side attached to a second side and a plurality of process arrays formed between the first and second sides. Each process array of the plurality of process arrays includes a loading structure, a main conduit with a length, and a plurality of process chambers distributed along the main conduit, wherein the main conduit is in fluid communication with the loading structure and the plurality of process chambers. The carrier includes a first surface facing the sample processing device and a second surface facing away from the sample processing device; and a plurality of openings formed through the first and second surfaces of the carrier, wherein each opening of the plurality of openings is aligned with one process chamber of the plurality of process chambers. The method further includes distributing sample material to at least some of the process chambers in each process array of the plurality of process arrays through the main conduit in each of the process arrays; locating the second side of the sample processing device in contact with a thermal block; selectively compressing the first side and second side of the sample processing device together proximate each process chamber of the plurality of process chambers, the selective compression occurring between the carrier and the thermal block; and controlling the temperature of the thermal block while the sample processing device is in contact with the thermal block.
In another aspect, the present invention provides a sample processing assembly including a sample processing device attached to a carrier. The sample processing device includes a body with a first side attached to a second side and a plurality of process arrays formed between the first and second sides. Each process array of the plurality of process arrays includes a loading structure, a main conduit with a length, and a plurality of process chambers distributed along the main conduit, wherein the main conduit is in fluid communication with the loading structure and the plurality of process chambers. The carrier includes a first surface facing the sample processing device and a second surface facing away from the sample processing device; a plurality of openings formed through the first and second surfaces of the carrier, wherein each opening of the plurality of openings is aligned with one process chamber of the plurality of process chambers; and a plurality of compression structures proximate the first surface of the carrier, each compression structure of the plurality of compression structures proximate one process chamber of the plurality of process chambers.
In another aspect the present invention provides a sample processing assembly that includes a sample processing device attached to a carrier. The sample processing device includes a body with a first side attached to a second side and a plurality of process arrays formed between the first and second sides. Each process array of the plurality of process arrays includes a loading structure, a main conduit with a length, and a plurality of process chambers distributed along the main conduit, wherein the main conduit is in fluid communication with the loading structure and the plurality of process chambers. Each process array also includes a deformable seal located between the loading structure and the plurality of process chambers in each process array of the plurality of process arrays. The carrier includes a first surface facing the sample processing device and a second surface facing away from the sample processing device; a plurality of main conduit support rails proximate the first surface of the carrier, wherein each main conduit of the plurality of process arrays is aligned with one main conduit support rail of the plurality of main conduit support rails; a plurality of openings formed through the first and second surfaces of the carrier, wherein each opening of the plurality of openings is aligned with one process chamber of the plurality of process chambers; and a plurality of compression structures proximate the first surface of the carrier, each compression structure of the plurality of compression structures proximate one process chamber of the plurality of process chambers.
In another aspect, the present invention provides a method of processing sample materials, the method including providing a sample processing assembly including a sample processing device attached to a carrier. The sample processing device includes a body with a first side attached to a second side and a plurality of process arrays formed between the first and second sides. Each process array of the plurality of process arrays includes a loading structure, a main conduit with a length, and a plurality of process chambers distributed along the main conduit, wherein the main conduit is in fluid communication with the loading structure and the plurality of process chambers. Each process array also includes a deformable seal located between the loading structure and the plurality of process chambers in each process array of the plurality of process arrays. The carrier includes a first surface facing the sample processing device and a second surface facing away from the sample processing device; a plurality of main conduit support rails proximate the first surface of the carrier, wherein each main conduit of the plurality of process arrays is aligned with one main conduit support rail of the plurality of main conduit support rails; and a plurality of openings formed through the first and second surfaces of the carrier, wherein each opening of the plurality of openings is aligned with one process chamber of the plurality of process chambers. The method further includes distributing sample material to at least some of the process chambers in each process array of the plurality of process arrays through the main conduit in each of the process arrays; closing the deformable seal in each process array of the plurality of process arrays, the closing including supporting the main conduit with one of the main conduit support rails while compressing the first side and the second side of the sample processing device together along at least a portion of the length of the main conduit; locating the second side of the sample processing device in contact with a thermal block; selectively compressing the first side and second side of the sample processing device together proximate each process chamber of the plurality of process chambers, the selective compression occurring between the carrier and the thermal block; and controlling the temperature of the thermal block while the sample processing device is in contact with the thermal block.
In another aspect, the present invention provides a method of processing sample materials, the method including providing a sample processing assembly including a sample processing device attached to a carrier. The sample processing device includes a body with a first side attached to a second side and a plurality of process arrays formed between the first and second sides. Each process array of the plurality of process arrays includes a loading structure, a main conduit with a length, and a plurality of process chambers distributed along the main conduit, wherein the main conduit is in fluid communication with the loading structure and the plurality of process chambers. Each of the process arrays also includes a deformable seal located between the loading structure and the plurality of process chambers in each process array of the plurality of process arrays. The carrier includes a first surface facing the sample processing device and a second surface facing away from the sample processing device; a plurality of main conduit support rails proximate the first surface of the carrier, wherein each main conduit of the plurality of process arrays is aligned with one main conduit support rail of the plurality of main conduit support rails; and a plurality of openings formed through the first and second surfaces of the carrier, wherein each opening of the plurality of openings is aligned with one process chamber of the plurality of process chambers. The method further includes distributing sample material to at least some of the process chambers in each process array of the plurality of process arrays through the main conduit in each of the process arrays; closing the deformable seal in each process array of the plurality of process arrays, the closing including supporting the main conduit with one of the main conduit support rails while compressing the first side and the second side of the sample processing device together along at least a portion of a length of the main conduit; separating the loading structure of each process array of the plurality of process arrays from the sample processing device; locating the second side of the sample processing device in contact with a thermal block; and controlling the temperature of the thermal block while the sample processing device is in contact with the thermal block.
In another aspect, the present invention provides a method of processing sample materials, the method including providing a sample processing assembly including a sample processing device attached to a carrier. The sample processing device includes a body with a first side attached to a second side and a plurality of process arrays formed between the first and second sides. Each process array of the plurality of process arrays includes a loading chamber, a main conduit with a length, and a plurality of process chambers distributed along the main conduit, wherein the main conduit is in fluid communication with the loading chamber and the plurality of process chambers. Each of the process arrays also includes a deformable seal located between the loading chamber and the plurality of process chambers in each process array of the plurality of process arrays. The carrier includes a first surface facing the sample processing device and a second surface facing away from the sample processing device; a plurality of main conduit support rails proximate the first surface of the carrier, wherein each main conduit of the plurality of process arrays is aligned with one main conduit support rail of the plurality of main conduit support rails; and a plurality of openings formed through the first and second surfaces of the carrier, wherein each opening of the plurality of openings is aligned with one process chamber of the plurality of process chambers. The method further includes distributing sample material to at least some of the process chambers in each process array of the plurality of process arrays through the main conduit in each of the process arrays; closing the deformable seal in each process array of the plurality of process arrays, the closing including supporting the main conduit with one of the main conduit support rails while compressing the first side and the second side of the sample processing device together along at least a portion of the length of the main conduit; separating the loading chambers of each process array of the plurality of process arrays from the sample processing device; selectively compressing the first side and second side of the sample processing device together proximate each process chamber of the plurality of process chambers, the selective compression occurring between the carrier and the thermal block; locating the second side of the sample processing device in contact with a thermal block; and controlling the temperature of the thermal block while the sample processing device is in contact with the thermal block.
In another aspect, the present invention provides an apparatus for closing deformable seals in a sample processing device that includes a plurality of process arrays formed between the first and second sides, wherein each process array of the plurality of process arrays includes a loading structure, a main conduit with a length, and a plurality of process chambers distributed along the main conduit, wherein the main conduit is in fluid communication with the loading structure and the plurality of process chambers, and further wherein each of the deformable seals is located between the loading structure and the plurality of process chambers in one process array of the plurality of process arrays. The apparatus includes a base with a cavity adapted to receive the sample processing device; a bridge operatively attached to the base, wherein the bridge is capable of traversing a sample processing device received in the cavity along a first direction; and a plurality of sealing structures mounted to the bridge, each of the sealing structures adapted to deform a portion of the sample processing device to close one of the deformable seals, wherein the plurality of sealing structures are aligned along the first direction such that each main conduit is sequentially deformed by the plurality of sealing structures.
In another aspect, the present invention provides a sample processing system including a sample processing device that includes a body with a first side attached to a second side and a plurality of process arrays formed between the first and second sides. Each process array of the plurality of process arrays includes a loading structure, a main conduit with a length, and a plurality of process chambers distributed along the main conduit, wherein the main conduit is in fluid communication with the loading structure and the plurality of process chambers. The system further includes a thermal block on which the sample processing device is located; and means for simultaneously and selectively compressing the first side and second side of the sample processing device together in a discrete area proximate each process chamber of the plurality of process chambers after locating the second side of the sample processing device in contact with a thermal block.
These and other features and advantages of the present invention are described below in connection with various illustrative embodiments of the devices and methods of the present invention.